The number of biologically active compounds useful as antivirals is very limited. Particularly limited are anti-HIV agents. Currently approved anti-HIV drugs include nucleoside analogs such as AZT. Unfortunately, recent results of a European trial of AZT in asymptomatic HIV-infected persons showed that administration of the drug caused no difference in survival after three years. In the face of slow progress on the development of an effective AIDS vaccine, a National Task Force on AIDS Drug Development has been established to explore new approaches to AIDS chemotherapy.
It is unlikely that a cure for AIDS will be discovered because HIV integrates itself into the host's genome and the main strategy to combat the disease is to keep the HIV virus from proliferating. At least 16 steps in the HIV life cycle have been identified as possible points for therapeutic intervention, yet all of the anti-HIV drugs licensed in the U.S. so far (AZT, ddI and ddC) are nucleoside inhibitors of HIV reverse transcriptase (RT). Rapid mutation of the virus presents a key challenge to antiretroviral drug therapy and AZT-resistant strains of HIV appear in patients after prolonged treatment. Non-nucleoside RT inhibitors are currently under investigation, but it is expected that combinations of drugs operating by different mechanisms will combat viral resistance most successfully. Hence, there is an urgent search for new drugs acting at different stages in the HIV life cycle. More recently discovered anti-HIV agents include certain bicyclams and quinolines such as quinoline-4-amine. The mechanism of action of the quinoline compound is unknown, but the bicyclams are reported to be inhibitors of HIV uncoating.
Another type of compound, the triaza macrocycles, have been used primarily for metal complexation. Previously, no biological activity has been suggested for these compounds.